Our goal is to gain further knowledge of the secretory immune system so as to enhance prospects for effective elicitation of secretory IgA antibody responses as immunoprophylaxis against infectious agents and environmental carcinogens. In the past year, we have concentrated on three aspects of the research program. First, in regard to the mechanism of homing of IgA plasma-cell precursors to mucosal sites, we have shown in a chemotactic assay system in vitro that the whey fraction of milk has selective chemotactic activity for mesenteric lymph node lymphocytes with surface IgA but not those with surface IgM or T cells. Second, we have purified disulfide interchange enzymes from human and rat sources. These will be compared and tested for their role in assembly of secretory IgA. Finally, we found that oral administration of protein can lead to a mucosal immune response, the formation of circulating antigen-IgA antibody immune complexes, and their deposition in the renal mesangium; this system, therefore, provides a model of human IgA nephropathy. Deposits with only IgA antibody do not lead to nephritis; however, admixture of IgG or IgM antibody promotes complement fixation and nephritis. (AB)